Research in the Goldstein lab focuses on computational modelling of pathogen evolution, with an emphasis on viruses.

In order to understand the properties of viruses, how they transmit, how they interact with their hosts, how they transfer between hosts, we need to investigate the evolutionary process that determined their form and function. Conversely, the evolution of viruses and hosts cannot be understood without considering how their form and function constrain the evolutionary process. Finally, the evolutionary record encodes the history of these organisms – when and where they emerged, how they spread amongst various populations, how they adapted to new hosts (such as humans), and how they have interacted with host factors, immune system, and drugs. Analysis of these sequences can provide a powerful window into this history, providing insight into the present situation and future trends. This has important consequences for monitoring and controlling disease emergence and spread, for identifying new drug targets, for modelling the emergence of drug resistance, as well as for developing our basic understanding of viruses and virus-host interactions.

We are engaged in three interrelated topics:

1) How do we understand the evolution of macromolecules such as genes and proteins? Using simple models of evolution, we try to develop a conceptual model for understanding the underlying evolutionary process, including the way the process depends upon its dynamically-changing context, that matches the growing available data on evolutionary change.

2) How can we use our understanding of macromolecular evolution to construct more realistic and informative models of evolutionary change? How can we construct models that allow us to better investigate the biology of the evolving systems, such as characterising the selective constraints acting on the genes and proteins, and how these change?

3) How can we apply these new models to important pathogens? How do we use these models to understand the interaction of viruses with their hosts, and how these interactions change when viruses jump hosts, particularly to humans? How do we determine transmission pathways, a matter of significance to public health efforts?

This work takes advantage of our placement in the Division of Infection & Immunity at UCL, providing us with a wealth of collaborative opportunities.